Down-regulation of {beta}-adrenergic receptors on mononuclear leukocytes induced by dobutamine treatment in patients with congestive heart failure

(±)-Dobutamine is a positive inotropic drug usually usedto improve ventricular function in patients with congestiveheart failure (CHF). However, it has been found that haemodynamicresponses to dobutamine become blunted during continuous treatment.In this study we determined the time-dependent changes of ß-adrenergicreceptors in CHF patients treated with dobutamine. Seven CHFpatients received a continuous intravenous infusion of dobutamine(5 µg.kg^–1. min^–1) for 96 h. Blood sampleswere obtained before and every 24 h after starting the therapy.The density of ß-adrenergic receptors on mononuclearleukocytes and the plasma concentrations of norepinephrine andepinephrine were determined. During dobutamine treatment thereceptor density (fmol.mg^–1, mean±SEM) graduallydecreased from 42.8±4.4 (baseline) to 31.4±3.3(P<0.05), 25.2±4.0 (P<0.01), 18.8±5.5 (P<0.01)and 13.4±3.4 (P<0.01) at 24, 48, 72 and 96 h, respectively.However, the plasma concentrations of norepinephrine and epinephrinewere not significantly changed during the 96 h period of treatment.Thus, the ß-adrenergic receptors down-regulated asearly as 24 h after the dobutamine treatment was begun in CHFpatients. This receptor down-regulation was not associated withchanges of plasma catechol-amine concentrations, but was relatedrather to the development of drug tolerance to dobutamine.